Studies of the oxidative degradation of picric acid (2,4,6-trinitrophenol) by H2O2 catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [Fe-III{4,5-Cl2C6H2-1,2-(NCOCMe2NCO)(2)CF2}(OH2)](-) (2) in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate or carbonate buffers and is not oxidized in their absence. The TAML- and buffer-catalyzed oxidation is subject to severe substrate inhibition, which results in at least 1000-fold retardation of the interaction between the iron(III) resting state of 2 and H2O2. The inhibition accounts for a unique pH profile for the TAML catalysis with the highest activity at pH 7. Less aggressive TAMLs such as [Fe-III{C6H4-1,2-(NCOCMe2NCO)(2)CMe2}(OH2)](-) are catalytically inactive. The roles of buffer components in modulating catalysis have been clarified through detailed kinetic investigations of the degradation process, which is first order in the concentration of 2 and shows ascending hyperbolic dependencies in the concentrations of all three participants, i.e., H2O2, picrate, and phosphate/carbonate. The reactivity trends are consistent with a mechanism involving the formation of double ([LFeIII-Q](2-)) and triple ([LFeIII-{Q-H2PO4}](3-)) associates, which are unreactive and reactive toward H2O2, respectively. The binding of phosphate converts [LFeIII-Q](2-) to the reactive triple associate. Density functional theory suggests that the stability of the double associate is achieved via both Fe-O-phenol binding and pi-pi stacking. The triple associate is an outer-sphere complex where phosphate binding occurs noncovalently through hydrogen bonds. A linear free energy relationship analysis of the reactivity of the mono-, di-, and trinitro phenols suggests that the rate-limiting step involves an electron transfer from phenolate to an oxidized ironoxo intermediate, giving phenoxy radicals that undergo further rapid oxidation that lead to eventual mineralization.